Empagliflozin in Acute Myocardial Infarction Reduces No-Reflow and Preserves Cardiac Function by Preventing Endothelial Damage

Panagiota Efstathia Nikolaou; Lara S F Konijnenberg; Ioannis V Kostopoulos; Marios Miliotis; Nikolaos Mylonas; Anastasios Georgoulis; George Pavlidis; Carolien T A Kuster; Vince P A van Reijmersdal; Tom T J Luiken; Anna Agapaki; Rona Roverts; Nikolaos Orologas; Dimitris Grigoriadis; Gaëtan Pallot; Pierre Boucher; Nikolaos Kostomitsopoulos; Michael Paul Pieper; Stéphane Germain; Yannis Loukas; Yannis Dotsikas; Ignatios Ikonomidis; Artemis G Hatzigeorgiou; Ourania Tsitsilonis; Coert J Zuurbier; Robin Nijveldt; Niels van Royen; Ioanna Andreadou

doi:10.1016/j.jacbts.2024.08.003

Empagliflozin in Acute Myocardial Infarction Reduces No-Reflow and Preserves Cardiac Function by Preventing Endothelial Damage

JACC Basic Transl Sci. 2024 Aug 30;10(1):43-61. doi: 10.1016/j.jacbts.2024.08.003. eCollection 2025 Jan.

Authors

Panagiota Efstathia Nikolaou^{1

2}, Lara S F Konijnenberg², Ioannis V Kostopoulos³, Marios Miliotis⁴, Nikolaos Mylonas¹, Anastasios Georgoulis¹, George Pavlidis⁵, Carolien T A Kuster², Vince P A van Reijmersdal², Tom T J Luiken⁶, Anna Agapaki⁷, Rona Roverts⁸, Nikolaos Orologas³, Dimitris Grigoriadis⁴, Gaëtan Pallot⁹, Pierre Boucher⁹, Nikolaos Kostomitsopoulos¹⁰, Michael Paul Pieper¹¹, Stéphane Germain⁹, Yannis Loukas¹², Yannis Dotsikas¹², Ignatios Ikonomidis⁵, Artemis G Hatzigeorgiou⁴, Ourania Tsitsilonis³, Coert J Zuurbier¹³, Robin Nijveldt², Niels van Royen², Ioanna Andreadou¹

Affiliations

¹ Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
² Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
³ Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Athens, Greece.
⁴ DIANA-Lab, Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia, Greece.
⁵ Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁶ Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.
⁷ Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
⁸ Electron Microscopy Center, Radboud UMC Technology Center, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
⁹ Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, PSL Research University, Paris, France.
¹⁰ Laboratory Animal Facilities, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
¹¹ Boehringer Ingelheim Pharma & Co., Mainz, Germany.
¹² Laboratory of Pharmaceutical Analysis, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
¹³ Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Amsterdam, the Netherlands.

Abstract

Empagliflozin treatment before acute myocardial infarction mainly targets the endothelial cell transcriptome. Empagliflozin treatment before and after myocardial infarction decreased no reflow and microvascular injury, leading to reduced infiltration of inflammatory cells, reduced infarct size, and improved cardiac function in mice. In diabetic patients receiving empagliflozin after myocardial infarction, perfused boundary region, flow-mediated dilation, and global longitudinal strain were improved.

Keywords: acute myocardial infarction; cardiac magnetic resonance; empagliflozin; microvascular injury; no-reflow.